Several studies suggest that gastritis, gastric ulcer and stress ulcer result from disruption of the mucosal barrier H ion. Although a variety of agents have been shown to increase mucosal permeability, little is known about the mechanism(s) which allow the stomach to maintain a high transmural gradient to H ion. Recent studies suggest that salicylate, but not bile salt or alcohol, increases permeability by altering field strength of the luminal border of isolated gastric mucosa. Sulfhydryl and amino groups of several membranes of nongastric tissues are important for maintenance of field strength, permeability and active transport processes. For gastric mucosa, both sulfhydryl and amino groups play a role in active ion transport, but amino groups appear to be more important determinants of permeability and appear to be unrelated to field strength effects. Pyridine compounds cause marked decreases in gastric mucosal permeability without significantly altering active transport. This study will continue to examine the effects of sulfhydryl and amino binding agents on active and passive cation and anion transport by gastric mucosa in order to determine the functional significance of amino and sulfhydryl ligands on ion transport. Sulfhydryl and amino reactive agents and pyridine compounds will be used singly and in combination in the presence and absence of salicylate, bile salt and alcohol in order to determine the nature of the sites important for the maintenance of permeability and alterations of ion transport. The results will allow determination of mechanisms for maintenance and alterations of mucosal permeability in vitro, which will then be correlated with in vivo studies using sulfydryl and amino reactive agents and pyridine compounds. In addition to gaining insight as to the nature of the gastric mucosal barrier, this investigation will also result in a better understanding of the complex inter-relationship among ion transport processes in the stomach as well as endocrine and metabolic regulation of ion transport in both fundus and antrum.